The aim of this project is to use electron probe x-ray microanalysis to determine the mechanism for entry of the anti-cancer drug cis-diamminedichloroplatinum II (cisplatin) into cancer cells, and how this entry is affected by drug resistance. Drug-sensitive and drug-resistant liver carcinoma cells were incubated for different times (0.5 hr, 1 hr, 2 hr, 4 hr) with 400 micromolar cisplatin and 100 micrograms/ml ferric chloride. The enzyme trypsin was used to release the cells gently from the culture dishes and to avoid damage by scraping. Cells were then pelleted, rapidly frozen in liquid ethane and cryosectioned. In the absence of cisplatin, cells prepared in this way were found to have normal Na/K gradients across the plasma membrane. Experiments are being performed on treated cells using x-ray microanalysis to co-localize cisplatin and iron.